Molecular Imaging and Biology

, Volume 13, Issue 2, pp 314–320

MRI with Magnetic Nanoparticles Monitors Downstream Anti-Angiogenic Effects of mTOR Inhibition

Authors

    • Center for Molecular Imaging Research, Department of RadiologyMassachusetts General Hospital
    • Center for Systems BiologyMassachusetts General Hospital
    • Division of Abdominal Imaging, Department of RadiologyMassachusetts General Hospital
  • Robert Ross
    • Lank Center for Genitourinary OncologyDana Farber Cancer Institute
  • Jose L. Figuereido
    • Center for Molecular Imaging Research, Department of RadiologyMassachusetts General Hospital
    • Center for Systems BiologyMassachusetts General Hospital
  • Peter Waterman
    • Center for Molecular Imaging Research, Department of RadiologyMassachusetts General Hospital
    • Center for Systems BiologyMassachusetts General Hospital
  • Ralph Weissleder
    • Center for Molecular Imaging Research, Department of RadiologyMassachusetts General Hospital
    • Center for Systems BiologyMassachusetts General Hospital
Research Article

DOI: 10.1007/s11307-010-0357-2

Cite this article as:
Guimaraes, A.R., Ross, R., Figuereido, J.L. et al. Mol Imaging Biol (2011) 13: 314. doi:10.1007/s11307-010-0357-2

Abstract

Purpose

To study the effect of mammalian target of rapamycin (mTOR) inhibition on angiogenesis with magnetic resonance imaging (MRI) using magnetic iron oxide nanoparticles (MNP).

Procedures

One million CAK-1 renal cell carcinoma cells were subcutaneously implanted into each of 20 nude mice. When tumors reached ∼750 μl, four daily treatment arms began and continued for 4 weeks: rapamycin (mTOR inhibitor) 10 mg/kg/day; sorafenib (VEGF inhibitor) high dose (80 mg/kg/day) and low dose (30 mg/kg/day); and saline control. Weekly MRI (4.7 T Bruker Pharmascan) was performed before and after IV MION-48, a prototype MNP similar to MNP in clinical trials. Vascular volume fraction (VVF) was quantified as ΔR2 (from multi-contrast T2 sequences) and normalized to assumed muscle VVF of 3%. Linear regression compared VVF to microvascular density (MVD) as determined by histology.

Results

VVF correlated with MVD (R2 = 0.95). VVF in all treatment arms differed from control (p < 0.05) and declined weekly with treatment. VVF changes with rapamycin were similar to high-dose sorafenib.

Conclusion

This study demonstrates noninvasive, in vivo anti-angiogenic monitoring using MRI of mTOR inhibition.

Key words

Magnetic resonance imagingMRIMagnetic nanoparticle imagingUltrasmall superparamagnetic iron oxide nanoparticleRenal cell cancermTORAngiogenesis

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010